miRNA GENETICS IN ALCOHOL ADDICTION As a trained physician and neuroscientist, the Candidate is committed to deepen knowledge about the molecular biology of alcohol addiction and to increase the treatment options for individuals suffering from alcohol abuse. The Candidate has recently discovered that microRNA (miR-9) has a crucial function in the development of alcohol tolerance in neurons of the Central Nervous System. These results are the very first example of the role of microRNA in alcohol actions in the brain. MicroRNAs belong to a family of endogenous, small, non-coding RNA species functioning as powerful regulators of gene expression. Each microRNA can function as a master-switch simultaneously modulating expression of multiple genes. Alcoholism is a disease of strong genetic component, and susceptibility to alcohol is influenced by multiple genes. The Candidate is dedicated to determine whether the development of alcoholism in human population is linked to miR-9 genes. The Candidate will take advantage of the availability of DNA samples collected from ethnically and genetically isolated groups of individuals addicted to alcohol and living on four different continents, and will apply human genetics methodology to identify polymorphism of miR-9 genes and their promoters. The long-term goal of these studies is to identify the single nucleotide polymorphisms (SNPs) in the regulatory regions of the miR-9 genes and in these genes themselves, and the contribution of these naturally occurring mutations to the activity of the miR-9 promoter regions, expression of miR-9 genes, and to the risk of the development of alcoholism in human population. Proposed studies will establish a role of miRNA in the development of alcoholism. The determination of this new mechanism can help to find out novel factors of the predisposition to alcoholism, as well as in early diagnostics of alcohol susceptibility, and can indicate novel therapeutic targets in alcohol abuse disorders.